Recognition Directed Site-Selective Chemical Modification of Molecularly Imprinted Polymers

Abstract

Demonstrated is the site-selective chemical modification (SSCM) of molecularly imprinted polymers (MIPs). In this strategy, MIPs are selectively chemically modified to improve the ratio of high-affinity to low-affinity binding sites and therefore the overall binding characteristics of the material. This was accomplished by preferentially eliminating the low-affinity binding sites by esterification with diazomethane or phenyldiazomethane. Selectivity in the esterification reaction was achieved using a guest molecule as an in situ protecting group that preferentially shields the high-affinity sites and leaves the low-affinity sites exposed toward reaction. The corresponding shifts in the populations of high- and low-affinity sites were quantified using affinity distribution analysis, which quantitatively measures the heterogeneous distribution of binding sites in MIPs as number of binding sites (N) with respect to binding affinity (K). Using affinity distribution analysis, the SSCM strategy was shown to improve the percentage of high-affinity sites in a methacrylic acid (MAA)/ethylene glycol dimethacrylate (EGDMA) matrix, imprinted with ethyl adenine-9-acetate (EA9A) in acetonitrile. The effects of different solvents and concentrations of guest molecule on the SSCM also were examined. The greatest improvements due to SSCM were observed when carried out in the imprinting solvent (acetonitrile). The demonstrated SSCM methodology is complementary to existing strategies for improving MIPs and thus can be utilized in tandem to improve the binding characteristics of MIPs.

Evaluation of molecularly imprinted polymers using 2′,3′,5′-tri-O-acyluridines as templates for pyrimidine nucleoside recognition

“…To circumvent this limitation, Manesiotis et al [16] used tetra-O-acyl riboflavins as 'dummy' templates to prepare a MIP against the polar vitamin riboflavin. Meanwhile, Lakka et al created a MIP-targeting adenosine using tri-Oacetyladenosine as 'dummy' template [17], while other authors have used 9-ethyladenine or adenine-9-acetate as a template for the same purpose [18,19].…”

Molecular imprinting science and technology: a survey of the literature for the years up to and including 2003

“…A similar approach has been used in the presence of bound template to modify the binding site distribution in favour of the higher affinity sites by selective poisoning of the low-affinity sites. 921,922 Esterification with blocking agents of different sizes has also been demonstrated to modify the binding properties of semi-covalently imprinted polymers. 507 The use of chiral ligands as poisons for imprinted catalysts has also been attempted.…”

“…Umpleby et al also proposed the affinity spectrum as a general description of the distribution of binding site affinity in MIPs, 481 and used this analysis to demonstrate that selective chemical modification of binding sites could alter the distribution in favour of higher affinity sites. 922 An earlier method of plotting the distribution of sites in terms of their chiral discriminating ability was published by Wulff et al 972 for covalent MIPs. Kim and Spivak 936 have used a method based on the Freundlich isotherm to investigate the effect of template concentration on the yield and stoichiometry of non-covalently imprinted sites.…”

Recent advances on noncovalent molecular imprints for affinity separations

“…In principle, this circumstance is considered detrimental to the application of MIPs in affinity-based chromatography, such as HPLC. The issue of binding site heterogeneity has been addressed by inactivating low affinity binding sites via esterification with appropriate blocking reagents such as diazomethane or phenyldiazomethane [4]. In this process, the template molecule is used as an in situ protecting reagent shielding the high affinity binding sites.…”